Life-threatening cardiovascular morbidity is a common clinical outcome for patients with obstructive sleep apnea syndrome (OSAS). To examine this relationship, our laboratory has developed a murine model of sleep-disordered breathing (SDB) that mimics major characteristics of OSAS, including chronic intermittent hypoxia (0H), frequent arousal, and sleep fragmentation. Preliminary research indicates that such long-term intermittent hypoxia results in both pulmonary and systemic hypertension, suggesting that SDB may indeed initiate and promote the development of cardiovascular morbidity. We are interested in examining genetic variation in the susceptibility to CIH-induced hypertension in a panel of common mouse strains. We propose that certain mouse strains will display greater acute ventilatory and hemodynamic responses to brief (<4min) hypoxic challenge and to changes in sleep/wake state. The first specific aim of this study will be to screen various strains of inbred mice for genetic differences in cardiovascular responses to brief hypoxic, hypercapnic, and combined hypoxic/hypercapnic challenges. The second specific aim will be to examine strain differences in hemodynamics during sleep stages. The third specific aim will address changes in hypoxic and hypercapnic responsiveness resulting from CIH treatment. Thus, in these studies we will characterize the sleep physiology and cardiovascular responses to hypoxia in several strains of mice, thereby contributing to the understanding of the link between acute hemodynamic effects and the cardiovascular pathology associated with SDB.